Introduction Despite rising concerns regarding the safety of anti-obesity medications, there is a lack of comprehensive pharmacovigilance investigations utilising real-world data. We aimed to characterise the prevalence and seriousness of adverse drug events (ADEs) related to anti-obesity medications and to identify predictors associated with increased risk of serious adverse events (SAE), thereby conveying evidence on drug safety. Methods We conducted a cross-sectional analysis on ADE cases spontaneously reported to the Korea Adverse Event Reporting System Database (KIDS-KD). ADE reports pertaining to anti-obesity medications prescribed for overweight, obesity (International Classification of Disease, 10th revision (ICD-10) code E66) and abnormal weight gain (ICD-10 code E63.5) were included in the analysis. We performed a disproportionality to detect the association of the system organ class-based ADEs with their seriousness an individual’s sex by estimating reporting odds ratios (RORs) and their 95% confidence intervals (CIs). We performed logistic regression to investigate factors that are substantially associated with increased SAE risks by estimating odds ratio (OR) and their 95% CIs. Results The most common causative anti-obesity medication was phentermine, followed by liraglutide. ADEs associated with psychiatric disorders (ROR=1.734; 95% CI=1.111-2.707), liver and biliary system disorders (ROR=22.948; 95% CI=6.613-70.635), cardiovascular disorders (ROR=5.707; 95% CI=1.965-16.574), and respiratory disorders (ROR=4.567; 95% CI=1.774-11.762) were more likely to be serious events. Additionally, men are more likely to experience ADEs related gastrointestinal disorders (ROR=1.411) and less likely to have heart and rhythm disorders (ROR=0.507). The risk of SAE incidences was positively correlated with being male (OR=2.196; 95% CI=1.296- 3.721), dual or triple combination of anti-obesity medications (OR=3.258; 95% CI=1.633-6.501 and OR=8.226; 95% CI=3.046-22.218, respectively), and concomitant administration of fluoxetine (OR=5.236; 95% CI=2.218-12.365). Conclusions Seriousness of anti-obesity medication-related ADEs differs among system-organ class, while sex-related differences in ADE profiles are also present. The predictors substantially increasing risk of SAE incidences include being male, having a higher number of concomitant medications (including multiple combination of anti-obesity medications), and concurrent use of fluoxetine. Nonetheless, further pharmacovigilance investigation and monitoring are needed to enhance awareness on ADEs induced by anti-obesity medications.
This study was supported by National Research Foundation Korea, funded by Ministry of Education (2021R1I1A1A01044500) and Ministry of Science and ICT (No. 2021R1C1C1003735), Mistry of Food and Drug Safety in 2023 (No. 21153MFDS 601), and Kyung Hee University in 2022 (KHU-20222123). YJ Choi received funds from Ministry of Education, Ministry of Food and Drug Safety, and Kyung Hee University. S. Shin received funds from Ministry of Science and ICT.Funding: This study was supported by National Research Foundation Korea, funded by Ministry of Education (2021R1I1A1A01044500) and Ministry of Science and ICT (No. 2021R1C1C1003735), Mistry of Food and Drug Safety in 2023 (No. 21153MFDS 601), and Kyung Hee University in 2022 (KHU-20222123). YJ Choi received funds from Ministry of Education, Ministry of Food and Drug Safety, and Kyung Hee University. S. Shin received funds from Ministry of Science and ICT. Authorship contributions: Conceptualization: YJC, CYC; Data curation: YJC, CUK, SS; Formal analysis: YJC; Funding acquisition: YJC, SS; Investigation: SS; Methodology: YJC, SS; Project administration: YJC, SS; Resources: YJC, SS; Software and supervision: YJC, SS; Validation: SS; Visualization: YJC, SS; Original draft: YJC; Writing-review and editing: YJC, SS. Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests. Additional material Online Supplementary Document 1 Safaei M, Sundararajan EA, Driss M, Boulila W, Shapi’i A. A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity. Comput Biol Med. 2021;136:104754. Medline:34426171 doi:10.1016/j.compbiomed.2021.104754 2 World Health Organization. Obesity and overweight. 2021. Available: https://www.who.int/news-room/fact-sheets/detail/ obesity-and-overweight. Accessed: 9 June 2021. 3 Centers for Disease Control and Prevention. Adult obesity facts. 2022. Available: https://www.cdc.gov/obesity/data/adult. html. Accessed: 2 May 2023. 4 Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab. 2020;11:2042018820934955. Medline:32612803 doi:10.1177/2042018820934955 5 Centers for Disease Control and Prevention. Obesity and cancer. 2023. Available: https://www.cdc.gov/cancer/obesity/in-dex.htm. Accessed: 2 May 2023. 6 Xu H, Cupples LA, Stokes A, Liu CT. Association of obesity with mortality over 24 years of weight history: Findings from the Framingham heart study. JAMA Netw Open. 2018;1:e184587. Medline:30646366 doi:10.1001/jamanetworkopen.2018.4587 7 Kolotkin RL, Meter K, Williams GR. Quality of life and obesity. Obes Rev. 2001;2:219-29. Medline:12119993 doi:10.1046/ j.1467-789X.2001.00040.xAcknowledgements: This study was supported by National Research Foundation South Korea, funded by Ministry of Education (2021R1I1A1A01044500) and Ministry of Science and ICT (No. 2021R1C1C1003735), Mistry of Food and Drug Safety in 2023 (No. 21153MFDS 601), and Kyung Hee University in 2022 (KHU-20222123) Ethical Statement: The pharmacovigilance study protocol utilizing the KIDS-KD ADE records was approved by Korea Institute of Drug Safety and Risk Management (Ministry of Food and Drug Safety) (No.2007A0051) and the institutional review board of Kyung Hee University (No. KHSIRB-22-486) (Seoul, South Korea). Informed consents were exempted by the board.
